Determination the concentration of norvancomycin and vancomycin in infected mice plasma by LC-MS/MS for the study of their pharmacokinetic properties
10.13699/j.cnki.1001-6821.2023.23.024
- VernacularTitle:用LC-MS/MS法测定感染小鼠血浆中去甲万古霉素及万古霉素的浓度及药代动力学研究
- Author:
Xi-Wei JI
1
;
Jia-Bin LIANG
;
Yun LI
Author Information
1. 北京大学第一医院临床药理研究所,北京 100191
- Keywords:
vancomycin;
norvancomycin;
liquid chromatography-mass spectroscopy;
blood concentration;
pharmaco-kinetics
- From:
The Chinese Journal of Clinical Pharmacology
2023;39(23):3455-3459
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish a rapid,sensitive method for the determination of vancomycin and norvancomycin in mice plasma and to investigate the pharmacokinetic(PK)characters of them in infected mice.Methods Propranolol was taken as the internal standard,the plasma samples were extracted by acetonitrile to precipitate protein.After centrifugation,the supernatant was analyzed by liquid chromatography-mass spectroscopy(LC-MS/MS).Chromatographic column:Kinetex Biphenyl 100A(2.1 mm ×50.0 mm,5 μm);mobile phase composed of methanol-water containing 0.2％formic acid in gradient elution mode;flow-rate of 0.4 mL·min-1;injection volume:10 μL.A triple quadrupole tandem mass spectrometer with electrospray ionization source was used as detector and operated by multiple reaction monitoring(MRM)in the positive ion mode.The specificity,standard curve,lower limit of quantification,precision and recovery,matrix effect,residual effect,dilution effect,and stability of this method were examined.The infected mice received three single oral doses(14,140 and 320 mg·kg-1)of vancomycin and norvancomycin and plasma samples were collected at different time points.Results The calibration curves of vancomycin and norvancomycin were linear between 50.0 and 3 000.0 ng·mL-1;the quantitation limit was 50 ng·mL-1;the intra-and inter-precision were ≤4.33％,≤18.26％and≤5.03％,≤15.19％,respectively;the extraction recovery were 80.61％to 109.38％and 83.94％to 97.34％,respectively;the intra-and inter-accuracy were-10.52％to 10.70％,-8.07％to 4.19％and-6.18％to 4.27％,-4.65％to 4.98％,respectively;and the matrix effects were 71.46％to 84.20％,and 85.64％to 93.11％,respectively.The results of methodological study of residual effect,dilution effect and stability conformed to the requirements.Conclusion A reliable LC-MS/MS method with high sensitivity,simple sample preparation and short elution time was developed for characterizing the PK profiles of vancomycin and norvancomycin in mice plasma.
